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Fibroblast-specific protein 1 (FSP1, also called S100A4) is considered a marker of fibroblasts in different organs undergoing tissue remodeling and is used to identify fibroblasts derived from EMT in several organs including the liver. The aim of this study was to characterize FSP1-positive cells in human and experimental liver disease. FSP1-positive cells were increased in human and mouse experimental liver injury including liver cancer. However, FSP1 was not expressed by HSC or type I collagen-producing fibroblasts. Likewise, FSP1-positive cells did not express classical myofibroblast markers, including \u03b1SMA and desmin, and were not myofibroblast precursors in injured livers as evaluated by genetic lineage tracing experiments. Surprisingly, FSP1-positive cells expressed F4\/80 and other markers of the myeloid-monocytic lineage as evaluated by double immunofluorescence staining, cell fate tracking, flow cytometry, and transcriptional profiling. Similar results were obtained for bone marrow-derived and peritoneal macrophages. FSP1-positive cells were characterized by increased expression of COX2, osteopontin, inflammatory cytokines, and chemokines but reduced expression of MMP3 and TIMP3 compared with Kupffer cells\/macrophages. These findings suggest that FSP1 is a marker of a specific subset of inflammatory macrophages in liver injury, fibrosis, and cancer.<\/jats:p>","DOI":"10.1073\/pnas.1017547108","type":"journal-article","created":{"date-parts":[[2010,12,20]],"date-time":"2010-12-20T23:23:52Z","timestamp":1292887432000},"page":"308-313","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":321,"title":["Fibroblast-specific protein 1 identifies an inflammatory subpopulation of macrophages in the liver"],"prefix":"10.1073","volume":"108","author":[{"given":"Christoph H.","family":"\u00d6sterreicher","sequence":"first","affiliation":[{"name":"Department of Medicine,"},{"name":"Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, and"},{"name":"Institute of Pharmacology, Center for Physiology and Pharmacology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melitta","family":"Penz-\u00d6sterreicher","sequence":"additional","affiliation":[{"name":"Department of Medicine,"},{"name":"Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, A-1090 Vienna, Austria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei I.","family":"Grivennikov","sequence":"additional","affiliation":[{"name":"Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Guma","sequence":"additional","affiliation":[{"name":"Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina K.","family":"Koltsova","sequence":"additional","affiliation":[{"name":"Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92093; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Datz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, General Hospital Oberndorf, A-5110 Oberndorf, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Sasik","sequence":"additional","affiliation":[{"name":"Biomedical Genomics Microarray Facility, Department of Medicine, University of California at San Diego, La Jolla, CA 92093;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Hardiman","sequence":"additional","affiliation":[{"name":"Biomedical Genomics Microarray Facility, Department of Medicine, University of California at San Diego, La Jolla, CA 92093;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Karin","sequence":"additional","affiliation":[{"name":"Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Brenner","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,12,20]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1126\/science.6828863","article-title":"Collagen formation by the hepatocyte in primary monolayer culture and in vivo","volume":"219","author":"Diegelmann RF","year":"1983","unstructured":"RF Diegelmann, PS Guzelian, R Gay, S Gay, Collagen formation by the hepatocyte in primary monolayer culture and in vivo. 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